Imagine being struck with a sudden onset of confusion, struggling to think of words or to recognize your surroundings — and even ending up in the emergency department because of it.
This may sound like the experiences of someone with dementia, but this description actually refers to a little-known but common complication that can arise from serious liver disease.
“Hepatic encephalopathy is one of the cardinal signs of liver failure,” Dr. Natasha Chandok, a hepatologist with the William Osler Health System, told CTVNews.ca in a phone interview earlier this year. “And it may be the sign that really impairs someone's quality of life, impacts their family, the most. So it's a very, very key sign of liver failure.”
Liver disease is the broad term for a number of conditions that damage the liver. Cirrhosis, a condition resulting from permanent scarring on the liver, can lead to liver failure.
Hepatic encephalopathy (HE), one of the main complications that can arise from cirrhosis, is a neurological issue that can leave patients reeling.
But although cirrhosis is common, the complexity of this often-stigmatized condition means that many people have never heard of HE before, even though it’s a red flag for liver failure.
“Encephalopathy can manifest with subtle things like personality changes, it can cause some neuromuscular dysfunction, it can cause difficulties sleeping at night and drowsiness in the daytime, which we call day-night reverse,” Chandok said. “When it is very, very extreme, it can even cause coma, and necessitate (intensive care unit) admission and intubation.”
Chandok, who is also an assistant clinical professor at McMaster University, takes care of patients with liver disease as well as patients before and after liver transplants. A huge part of the job is trying to educate both patients and family members on what to expect with cirrhosis, including complications such as HE.
Ensuring family members can recognize the signs is one of the most important things, as they will often be the ones to notice first when a cirrhosis patient is beginning to experience more severe symptoms of HE, she explained.
“Very often, as you can imagine, if someone is confused, they may not have the self-awareness to realize that there are some changes,” she said. “And we really want to hit home with that caregiver education.”
Dr. Vladimir Marquez, a gastroenterologist and transplant hematologist expert from Vancouver General Hospital, explained that when the liver is unable to perform its regular function and filter toxins out of the blood, those toxins will eventually make their way into the brain, which is how HE happens.
"Some of (the toxins) will create disruptions of the blood-brain barrier, some of them will actually penetrate into cells, creating different types of deposits on brain cells that will affect their function,” he told CTVNews.ca in a phone interview in early 2023.
And patients experiencing this can have symptoms come on fast.
“There are patients that in some situations can wake up being completely fine, but during the course of the day they become actively confused,” Marquez said. “It's not necessarily a continuum, meaning that a patient will go through one stage and then the other and then the other — patients can manifest symptoms of severity of any stage at any moment, although usually in the early stages of their disease, they will usually present the more subtle signs.”
The fact that liver damage can be connected to alcohol abuse means that there is a significant amount of stigma still surrounding liver disease, something which Chandok believes impacts awareness of the issue and how it can present medically.
“People with liver disease are stigmatized,” Chandok said. “Liver patients don't get the funding that oncology does or that cardiac disease does. People really look down, unfortunately, on people with cirrhosis. They have certain biases and attitudes that unfortunately, I think, infiltrate into funding.”
THE REALITIES OF CIRRHOSIS
Cirrhosis is a serious issue in Canada — one Ontario study suggests that around one in four Canadians may have chronic liver disease and be at risk of developing cirrhosis at some point in their lives.
By the time a patient has been diagnosed with cirrhosis, treatment is aimed at preventing the condition from worsening and maintaining a good quality of life. Generally, there is no solution for cirrhosis outside of a liver transplant, and not everyone is eligible, with long lines waiting for those who are.
“Most people in Canada, most patients with cirrhosis, less than 10 per cent will actually move on to a transplant, and that’s because a liver transplant has many contraindications,” Chandok said.
Not all types of liver disease will result in cirrhosis. For instance, those with fatty liver disease, which is common in Canada, are unlikely to develop cirrhosis.
Every time your liver is damaged — through chronic alcohol abuse, conditions such as hepatitis, infection or various forms of liver disease — the tissue tries to repair itself. But the liver can only accumulate so much scar tissue before the organ begins to struggle to do its job.
This triggers symptoms including jaundice, spider-like blood vessels visible on the skin and fatigue, along with the potential for serious complications, including fluid retention in the abdomen (called ascites), enlarged veins bursting inside the body and patients vomiting blood or experiencing “black, tarry stool.”
“That happens because when the liver is scarred, we basically can't drain blood from our stomach and esophagus,” Chandok explained. This type of bleeding is called gastrointestinal, or GI, bleeding.
HE is generally only a symptom “that one would experience if one has cirrhosis,” Chandok explained.
But it’s far from rare among cirrhosis patients, experts say.
“It will probably be observed in over 50 per cent of patients with liver disease, although at different degrees of severity,” Marquez said.
The more serious the cirrhosis, the more common HE is, with this condition “extremely common” in patients with decompensated cirrhosis, which is the moderate or severe group, Chandok said.
“It’s one of those three things we look for to see: ‘Does our patient need a transplant?”
WHAT MAKES HE SUCH A HURDLE
The wide range of how HE presents — from mild confusion to a coma-like state — makes finding the trigger and addressing it a huge concern that bring a burden to both the patient and the health-care system.
Although HE can occur purely from cirrhosis, usually HE in cirrhosis patients is triggered by something specific. This might be an infection, or bleeding related to the cirrhosis, or even a case of COVID-19.
“They could have a urine infection,” Chandok said. “And because their liver is not functioning well, that strain on the liver will trigger and encephalopathy.”
“Common causes could be infection, dehydration, low potassium level. If left untreated, especially because we know often there's an underlying cause to it, patients usually deteriorate. So having neurological changes is one of the cardinal symptoms that we ask patients and their families to look for. And frequently the patient has to present to the emergency room, because it can be very, very fatal.”
Even mild HE can significantly impact a patient’s quality of life, as it’s distressing to experience neurological symptoms and the loss of independence that comes with it.
For instance, once patients have been diagnosed with HE, they should not be driving anymore, Marquez said, because “it could be unsafe.”
“(It’s) one symptom that I feel impacts the patient the most, often in the family, because the neurological changes, it’s very frightening for families,” Chandok added.
Currently, there is treatment to help prevent HE in cirrhosis patients and to stop it from worsening, but this treatment brings its own complications.
One option is a laxative with specific properties to help eliminate nitrogenous wastes from the colon and lower ammonia production.
Too much ammonia in the bloodstream due to the patients’ inability to filter their blood through their liver can contribute to HE.
The other treatment available is an antibiotic that stays in the gut and works on eliminating bacteria in the colon to stop ammonia production that way.
However, many patients have difficulty keeping up with their medication on a daily basis due to a lack of knowledge on how important it is, Chandok said.
Keeping up with a prescription for a laxative such as Lactulose, will help patients from experiencing serious HE and hopefully keep them out of the emergency room, but many patients don’t grasp the scope of the issue.
“The problem with Lactulose is that it has a lot of side effects that are very difficult to manage by patients on a daily basis,” Marquez said.
Doses vary by person and side effects can include feeling uncomfortable, bloated or gassy.
“It's very common for patients to say, ‘I stopped taking my Lactulose,’” Chandok added. “And then, lo and behold, three days later, they're in the emergency room with encephalopathy. So if there is a lot of education that needs to be involved with staying compliant with (medication).”
An antibiotic called Rifaximin is better tolerated than Lactulose, but is sometimes less accessible to patients, depending on region and supplies, Chandok said.
When cirrhosis patients either fall behind on their medication or develop serious HE despite medication, it balloons into a much larger issue, which is part of the reason experts want to emphasize awareness of this specific cirrhosis complication.
“When patients come to the emergency room with encephalopathy, the amount of nursing care that is needed for the patient is astronomical,” Chandok said.
Patients will need Lactulose every half an hour to an hour, and sometimes are not able to take it orally due to how sick they are, which means more intensive routes to get the medication into their bodies.
“Nurses are angels, but they're overworked, and it's very hard to manage that,” Chandok said. “The cirrhotic patient needs so much nursing care. So we really want to do what we can to prevent admission.”
PANDEMIC IMPACTS AND MOVING FORWARD
The COVID-19 pandemic shook the health-care system with a force that is still being felt in 2023, causing massive worker burnout and delays to certain tests and procedures.
“The lack of in-person care led to less monitoring, so less blood work, less ultrasounds,” Chandok said. "In my own practice, I noticed very scary findings that there were a lot more cases of liver cancer because people had delayed their screening ultrasounds for liver cancer.”
She added that some data showed an increase in alcohol abuse during the pandemic, something that could have ripple effects.
“That makes me concerned about from a population level, the risks of liver cancer and the risks of cirrhosis,” she said.
The number of organ donations and transplants did rebound in 2021 after the number dropped sharply in 2020, according to the Canadian Institute for Health Information, but the wait time for liver transplants was still the second deadliest, with 95 patients dying while waiting for a liver in 2021.
As the health-care system seeks to restructure, Chandok believes that the answer to addressing the complex needs of a patient with cirrhosis is a more multidisciplinary approach.
That’s something she’s been working on through the development of a “multidisciplinary complex cirrhosis clinic.”
It’s a project that she is hoping could provide a model for better treatment in the future.
“I've come to feel that cirrhosis is best managed with a team because patients are so complex,” she said.
“So patients who have encephalopathy in the hospital or had other cardinal events like variceal bleeding, when they leave the hospital, we have them have an early appointment (with) this team clinic, where we have access to all these wonderful Allied Health member teams.”
Patients with fatty liver disease, for instance, would really benefit from having a dietician to help balance certain aspects of their diet for their health, as well as a physical therapist, Chandok said.
At the clinic, they’ve also been able to offer patients literature in their own language, and have translation services as well in order to ensure patients have the full understanding of how to keep up with their medication, and the reason why it’s so important to stay on track with them.
In addition, they can connect patients who are struggling with addiction with the resources they need all under one roof.
“We really work with the patient to make sure they're filling their scripts, they're taking their medicines, they know how to take their medicine,” Chandok said.
“I hope a model like we've made with our interdisciplinary complex liver clinic can be something that can be funded. It’s not right now, so I'm relying on volunteerism and kind of the goodness of people to really prioritize our patients.”